This invention relates to a bacteria- and immunoglobulin-containing composition and methods of use thereof for promoting gastrointestinal health. More particularly, the invention relates to a composition comprising living bacteria that are beneficial for gastrointestinal health and an immunoglobulin preparation containing immunoglobulins that are capable of binding and inactivating foreign antigens such as pathogenic bacteria, viruses, fungi, and protozoa that are detrimental to gastrointestinal health.
Since the time of Hippocrates and throughout the Middle Ages, large doses of whey were prescribed by alchemists for treating many ailments, primarily acute septic conditions. Although it was not then known the reason that whey was useful for treating such conditions, recent studies have shown that whey contains antibodies or immunoglobulins capable of providing passive immunity against various pathogens and their toxic by-products. Antibodies or immunoglobulins are high molecular weight proteins produced in the bodies of mature animals that enhance immunity to infection by bacteria, viruses, fungi, protozoa, and the like. Antibodies in human and bovine milk promote development of a healthy gastrointestinal tract and provide protection against infections by pathogenic microorganisms. These antibodies interfere with the process that allows such pathogenic microorganisms to adhere to and colonize the intestinal lining. Studies have shown that immunoglobulins from whey are particularly effective against viruses (e.g. rotavirus), bacteria (E. coli, Vibrio cholerae, Salmonella), fungi (Candida), and protozoa (Cryptosporidium).
Detectable levels of anti-rotavirus antibodies (IgG.sub.1) have been found in raw and pasteurized milk. R. H. Yolken, Antibody to Human Rotavirus in Cow's Milk, 312 New Eng. J. Med. 605 (1985). The high temperatures used in processing infant formula, however, destroy all traces of naturally occurring IgG.sub.1. Many infants develop gastroenteritis around 6 months of age, about the time they are weaned from breast milk and started on formula.
Since infants and young children are highly susceptible to gastroenteritis, treatment of acute diarrhea with concentrated immunoglobulins has been investigated. In one study, infants hospitalized with acute rotavirus gastroenteritis were treated with an immunoglobulin concentrate derived from rotavirus-immunized cows. H. Hilpert et al., Use of Bovine Milk Concentrate containing Antibody to Rotavirus to Treat Rotavirus Gastroenteritis in Infants, 156 J. Infect. Dis. 158 (1987). These infants showed significantly reduced duration of rotavirus excretion. Thus, bovine milk immunoglobulin provided passive immunity against rotavirus gastroenteritis in human infants.
A bovine milk immunoglobulin concentrate derived from E. coli-immunized cows has also been shown to inhibit colonization of enteropathic E. coli in affected infants. C. Mietens et al., Treatment of Infantile E. Coli Gastroenteritis with Specific Bovine Anti-E. Coli Milk Immunoglobulins, Eur. J. Pediatrics (1979). Stool samples showed a reduction in E. coli counts and the duration of diarrhea was shortened, demonstrating that this concentrate was effective in treating infantile diarrhea.
Inflammation of the gastrointestinal mucosa and diarrhea associated with Traveler's Diarrhea due to E. coli infection have been prevented by treatment with an immunoglobulin concentrate from bovine milk. C. Tackether al., Protection by Milk Immunoglobulin Concentrate against Oral Challenge with Enterotoxigenic Escherichia Coli, 318 N. Engl. J. Med. 1240 (1988).
Immunoglobulins from bovine colostrum have been shown to be an effective treatment for diarrhea due to a pathogenic protozoan, Cryptosporidium. S. Tzipori et al., Remission of Diarrhoea Due to Cryptosporidiosis in an Immunodeficient Child Treated with Hyperimmune Bovine Colostrum, 293 Br. Med. J. 1276 (1986). Immunodeficient individuals, particularly those with acquired immune deficiency syndrome (AIDS) are especially susceptible to cryptosporidiosis.
Certain bacteria have also been shown to be beneficial to human gastrointestinal health. Bacteria of the genus Lactobacillus have been used for several hundred years for treating various illnesses. Lactobacilli found in the human intestinal tract include L. acidophilus, L. casei, L. fermentum, L. salivaroes, L. brevis, L. leichmannii, L. plantatum, and L. cellobiosus. In recent years, L. acidophilus has been shown to be exceptionally useful in treating conditions such as antibiotic-induced imbalances in the gastrointestinal microflora, hypercholesterolemia, vaginal infections, E. coli infection, oral contraceptive failure, depressed immunity, cancerous tumors, chronic granulomatous disease, and lactose indigestion. A. G. Shauss, Method of Action, Clinical Application, and Toxicity Data, 3 J. Advancement Med. 163 (1990). In vitro studies have shown L. acidophilus to have an inhibitory effect on the growth of pathogenic bacteria such as Campylobacter pylori, Staphylococcus aureus, Pseudomonas aeruginosa, and Sarcina lutea. K. M. Shahani et al., Natural Antibiotic Activity of Lactobacillus Acidophilus and Bulgaricus, 11 Cultured Dairy Products J. 14 (1976).
The beneficial effect of L. acidophilus is further illustrated by preliminary evidence that L. acidophilus inhibits the toxic activities of bacteria in patients with chronic kidney failure. M. L. Simenhoff et al., Biomodulation of Uremic Pathophysiology in Man, abstract presented at Am. Soc. of Nephrology Meeting, Baltimore, 1992. Such patients often have toxic levels of amines in their blood due to bacterial overgrowth in the small bowel. Consumption of high levels of freeze dried bacteria drastically reduced levels of these toxic amines. These results demonstrate the ability of L. acidophilus to exert a positive effect on the microflora of the intestines.
It has also been shown that the activities of fecal bacterial enzymes thought to play a role in conversion of procarcinogens to carcinogens, such as beta-glucuronidase, nitroreductase, and azoreductase, were reduced 2- to 4-fold in subjects taking L. acidophilus supplements. B. R. Goldin & L. S. Gorbach, The Effect of Milk and Lactobacillus Feeding on Human Intestinal Bacterial Enzyme Activity, 39 Amer. J. Clin. Nutr. 756 (1984). These results suggest that dietary supplementation with L. acidophilus may reduce the risk of developing colon cancer.
Bifidobacteria are also known to exert a beneficial influence on human health. These bacteria exert antimicrobial activity in the human intestine by producing lactic acid and acetic acid as a result of carbohydrate metabolism. These acids lower the intestinal pH, thereby inhibiting overgrowth of gastrointestinal pathogens. Therapeutic applications of bifidobacteria are indicated for the management of diarrhea and constipation, and the management of hepatic encephalopathy with hyperammonemia. Additional benefits include the production of B vitamins and breakdown of carcinogenic N-nitrosamines.
Bifidobacterium adolescentis is the predominant species of bacteria in humans after age two. This predominance suggests its exceptional stability and prolonged proliferation in the intestine. Nevertheless, for any preparation of living microorganisms to function as a commercial dietary supplement, in addition to being able to provide a beneficial effect must also exhibit good survival in storage, resistance to inactivation by bile, and survival through the gastrointestinal tract. Strain-to-strain or isolate-to-isolate variability can occur as to these traits, thus the selected properties should be verified before commercializing any particular product containing such microorganisms.
In view of the foregoing, it will be appreciated that a composition for improving gastrointestinal health comprising living bacteria that exert a beneficial effect on the gastrointestinal tract and an immunoglobulin preparation containing immunoglobulins that bind and inactivate pathogenic microorganisms in the gastrointestinal tract would be a significant advancement in the art.